The basis for the increased susceptibility of the aged to infections will be studied from the standpoint that a progressive decrease occurs during aging in the ability of cells in the immune system to function together and to interact for the purpose of an effective immune response to challenge. An integrated approach is planned in which receptors of lymphoid cells and lymphokine production and/or responsiveness will receive particular attention, as they represent the major means by which lymphoid cells communicate. One project concerns the effect of aging on the proliferative and regenerative capacity of memory B cells as related to the generation of germinal centers in lymphoid tissue of mice. The second project analyzes the surface properties, numbers and functional activities of Langerhans cells in the skin of aged mice and humans and the ability of these cells to return to normal after exposure to agents such as UV-irradiation and corticosteroids. The third project focuses on the functional activity and interrelation between various T cell subsets in mice, including lymphokine production, cytotoxic and suppressor activities. The fourth project proposes to study the ability of the thymus in aged mice to regenerate in response to injury, to receive immigrant prothymocytes and to support their differentiation. In the fifth project a study will be made, in humans and mice, of the relationship between the production of IL-1 and the ability of the aged to respond with fever to infections, as well as of the influence of corticosteroid production in response to stress on this process.